Learn More
While timely reperfusion of acute ischemic myocardium is essential for myocardial salvage, reperfusion results in a unique form of myocardial damage. Functional alterations occur, including depressed contractile function and decreased coronary flow as well as altered vascular reactivity. Both myocardial stunning and infarction are seen. Over the last two(More)
We performed experiments in dog ventricular trabeculae loaded with aequorin to elucidate the mechanism of positive inotropic effect of (R)-N-[4-(4-methyl-6-oxo-1,4,5, 6-tetrahydro-pyridazin-3-yl)-phenyl]-acetamide (OR-1896), an active metabolite of (R)-([4-(1,4,5, 6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]-hydrazono)-pr opaned initrile(More)
We performed experiments in rabbit ventricular papillary muscles loaded with aequorin to elucidate the mechanism of positive inotropic effect (PIE) of OR-1896, an active metabolite of levosimendan. The concentration-response curve (CRC) for OR-1896 was biphasic: PIE of OR-1896 reached a plateau at 10(-5) M (first phase), and the CRC became steeper at 10(-3)(More)
Effects of levosimendan on myocardial contractility and Ca2+ transients were assessed in the ventricular myocardium of the rabbit. Levosimendan at and above 0.1 microM had a concentration-dependent positive inotropic effect (PIE) on isolated papillary muscles that had been loaded with aqeuorin. The maximum inotropic response to levosimendan at 3 microM was(More)
Endothelin (ET) isopeptides, ET-1, ET-2 and ET-3, elicit a positive inotropic effect (PIE) in association with a negative lusitropic effect, essentially with identical efficacies and potencies in the isolated rabbit papillary muscle, but with different concentration-dependent properties. Pharmacological analysis indicates that the PIE of ET-1 is mediated by(More)
To clarify the relative roles of A(2) adenosine receptor subtypes in the regulation of coronary flow and myocardial contractility, coronary vascular and functional responses to adenosine and its analogs were examined in isolated wild-type (WT) and A(2A) receptor knockout (A(2A)KO) mouse hearts. Nonselective agonists adenosine and(More)
The present study was designed to characterize and compare the vascular effects of adenosine and its analogs in the murine heart and aorta. Mouse hearts perfused under constant pressure in standard Langendorff fashion demonstrated concentration-dependent increases in coronary flow to adenosine, 2-chloradenosine (CAD), 5'-(N-ethyl-carboxamido)-adenosine(More)
Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(•-)), which are key mediators of cellular signalling. In the presence of Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l-arginine (l-Arg) by means of electron transfer from(More)
Endothelin-1 (ET-1) increased cell shortening and Ca2+ transients over the concentration of 3 x 10(-11) M to 10(-9) M with EC50 of 8.3 x 10(-11) M in rabbit single ventricular myocytes. Thus ET-1 was approximately 60 times more potent in single myocytes than in papillary muscles (EC50 = 5.1 x 10(-9) M) of the same species. In single myocytes, ET-1 at 10(-8)(More)
The present study was designed to delineate pharmacologically the role of sarcolemmal L-type Ca2+ channels and Na+/H+ exchange in the positive inotropic effect (PIE) of phenylephrine mediated by alpha-1 adrenoceptors, endothelin (ET) and angiotensin II (Ang II) that stimulate phosphoinositide (PI) hydrolysis in the rabbit ventricular muscle. The PIE of(More)